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Structural Basis for the Identification of an i‐Motif Tetraplex Core with a Parallel‐Duplex Junction as a Structural Motif in CCG Triplet Repeats
Author(s) -
Chen YiWen,
Jhan CyongRu,
Neidle Stephen,
Hou MingHon
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201405637
Subject(s) - motif (music) , stacking , duplex (building) , structural motif , cytosine , chemistry , crystallography , base pair , dna , stereochemistry , biochemistry , physics , organic chemistry , acoustics
CCG triplet repeats can fold into tetraplex structures, which are associated with the expansion of (CCG) n trinucleotide sequences in certain neurological diseases. These structures are stabilized by intertwining i‐motifs. However, the structural basis for tetraplex i‐motif formation in CCG triplet repeats remains largely unknown. We report the first crystal structure of a CCG‐repeat sequence, which shows that two dT(CCG) 3 A strands can associate to form a tetraplex structure with an i‐motif core containing four C:C + pairs flanked by two G:G homopurine base pairs as a structural motif. The tetraplex core is attached to a short parallel‐stranded duplex. Each hairpin itself contains a central CCG loop in which the nucleotides are flipped out and stabilized by stacking interactions. The helical twists between adjacent cytosine residues of this structure in the i‐motif core have an average value of 30°, which is greater than those previously reported for i‐motif structures.